Characterizing the emergence of amyloid and tau burden in Down syndrome.

INTRODUCTION

Almost all individuals with Down syndrome (DS) will develop neuropathological features of Alzheimer's disease (AD). Understanding AD biomarker trajectories is necessary for DS-specific clinical interventions and interpretation of drug-related changes in the disease trajectory.

METHODS

A total of 177 adults with DS from the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) underwent positron emission tomography (PET) and MR imaging. Amyloid-beta (Aβ) trajectories were modeled to provide individual-level estimates of Aβ-positive (A+) chronicity, which were compared against longitudinal tau change.

RESULTS

Elevated tau was observed in all NFT regions following A+ and longitudinal tau increased with respect to A+ chronicity. Tau increases in NFT regions I-III was observed 0-2.5 years following A+. Nearly all A+ individuals had tau increases in the medial temporal lobe.

DISCUSSION

These findings highlight the rapid accumulation of amyloid and early onset of tau relative to amyloid in DS and provide a strategy for temporally characterizing AD neuropathology progression that is specific to the DS population and independent of chronological age.

HIGHLIGHTS

Longitudinal amyloid trajectories reveal rapid Aβ accumulation in Down syndrome NFT stage tau was strongly associated with A+ chronicity Early longitudinal tau increases were observed 2.5-5 years after reaching A.